PXD066933

PXD066933 is an original dataset announced via ProteomeXchange.

Title	Characterisation of the Active Kinome of Leishmania
Description	Background: Leishmania parasites cause neglected tropical diseases such as cutaneous and visceral leishmaniasis, which have limited treatment options and rising drug resistance. Protein kinases are pivotal in Leishmania biology and attractive drug targets, but their functional status in the parasite remains largely unexplored. Methods: We applied activity-based protein profiling (ABPP) with custom in-house cell-permeable ATP-site directed probes to map the “active kinome” of Leishmania mexicana. Three related covalent probes featuring an ATP-mimetic scaffold, electrophilic warhead (targeting catalytic lysines or cysteines), and alkyne tag were synthesised to broadly capture active kinases. Live parasites were labelled with probes, followed by click-chemistry tagging, in-gel fluorescence, and tandem mass tag (TMT) proteomics for kinase identification and quantification. Comparative profiling was performed across Leishmania species and life stages. Key findings were validated by competition experiments with ibrutinib and parasite viability assays. Results: We uncovered 16 metabolic kinases and 32 protein kinases spanning all major kinase families (CMGC, AGC, STE, CAMK, CK1, and NEK), including 9 protein kinase enzymes encoded by essential genes and several kinases lacking human orthologs. Notable hits included CRK1, MPK4, CK1.2, and an atypical kinase, underscoring their potential as drug targets. Conclusion: This study provides the first ABPP survey of the Leishmania kinome, revealing multiple active kinases that drive parasite survival and virulence. Our chemoproteomic approach highlights both essential protein kinases and unique metabolic kinases as a rich source of potential drug targets. These findings demonstrate that ABPP can unveil the biochemically active kinases in Leishmania, offering a new strategy for prioritizing kinase targets and accelerating kinase inhibitor development against leishmaniasis. The work lays a foundation for next-generation antileishmanial therapies directed at the parasite kinome, particularly those kinases indispensable for the parasite yet sufficiently divergent from the human host.
HostingRepository	PRIDE
AnnounceDate	2025-12-18
AnnouncementXML	Submission_2025-12-18_06:38:28.443.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karunakaran Kalesh
SpeciesList	scientific name: Leishmania mexicana; NCBI TaxID: NEWT:5665;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-04 08:05:03	ID requested
⏵ 1	2025-12-18 06:38:28	announced

Dataset with its publication pending

submitter keyword: parasite, drug target,Leishmania, chemoproteomics, neglected tropical disease, activity-based protein profiling, protein kinase, kinome

Kalesh Karunakaran
contact affiliation	School of Health and Life Sciences, Teesside University, UK
contact email	k.karunakaran@tees.ac.uk
lab head
Karunakaran Kalesh
contact affiliation	Teesside University
contact email	k.karunakaran@tees.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/12/PXD066933

PRIDE project URI

• PRIDE
  1. PXD066933
     1. Label: PRIDE project
     2. Name: Characterisation of the Active Kinome of Leishmania